Baseline Assessment of Skin Resident Memory T Cells in Healthy Unvaccinated Participants

Baseline Assessment of Skin Resident Memory T Cells in Healthy Unvaccinated Participants (GeKoSkimm-Unvaccinated): add-on Study to the GeKoSkimm Trial (= A Randomized Controlled Trial to Compare the Immunogenicity and Skin Imprinting of Intradermal, Subcutaneous and Intramuscular Yellow Fever Vaccination)

In The main GeKoSkimm trial (= A randomized controlled trial to compare the immunogenicity and skin imprinting of intradermal, subcutaneous and intramuscular yellow fever vaccination) the investigators try to understand whether the route of injection (in the muscle, under the skin, or in the skin) when giving the yellow fever vaccine affects the strength of the body's immune response to yellow fever. More in particular the investigators want to know how well the immune responses are retained in the skin, as this is the place where the virus enters the body after a mosquito bite. This will be important for vaccines against infections transmitted via bites of mosquitoes and ticks, such as yellow fever virus. Because this is the first attempt on human samples and only skin samples after vaccination with yellow fever vaccine are available, the investigators want to assess the baseline or background immune response in 'unvaccinated' skin. Therefore, 40 volunteers will be recruited that have not been previously vaccinated against yellow fever and will not receive a yellow fever vaccine during this study. The participant will be requested to provide two skin samples from the upper arm and a blood sample to confirm their vaccination status regarded to yellow fever.

Study Overview

• Status: Not yet recruiting
• Conditions: Yellow Fever (Healthy Volunteers); Biopsy/Methods
• Intervention / Treatment: Procedure: Skin punch biopsy; Procedure: Blood samples

Detailed Description

Since baseline punch biopsies were not preferred nor incorporated in the GeKoSkimm trial (= A randomized controlled trial to compare the immunogenicity and skin imprinting of intradermal, subcutaneous and intramuscular yellow fever vaccination) due to ethical and logistical reasons, studying tissue-resident memory T (TRM) cells in a group of healthy unvaccinated participants is necessary to assess natural baseline levels of TRM cells in the skin before vaccination. The presence TRM cells in healthy and unvaccinated individuals provides a fundamental understanding of normal immune function and biological variability. This baseline data is essential for interpreting responses to vaccination in the GeKoSkimm trial and detecting any deviations or abnormalities that may arise and assess the baseline or background immune response in 'unvaccinated' skin. Therefore, 40 volunteers will be recruited that have not been previously vaccinated against yellow fever and will not receive a yellow fever vaccine during this study. The study consists of two study visits with 14 days (+/- 10 days) between each visit. Blood sampling of 15 mL is performed on the first visit (1X 10 mL Li-Hep + 5 mL SST) to confirm the vaccination status against yellow fever virus (YFV). Participants who turn out positive on the YFV virus neutralization test will be retrospectively excluded from analyses, and replaced with new participants. Skin biopsy sampling (2X 4 mm punch biopsy) in the upper arm is performed only on the second visit, with additional microsampling (microbiopsy and wound blood sampling).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Prof. Dr. Patrick Soentjens; Phone Number: +3232476641; Email: psoentjens@itg.be
• Study Contact Backup: Name: Wim Adriaensen; Email: wadriaensen@itg.be

Study Locations

• Belgium
  • Antwerp, Belgium
    • Clinical Trial Site of the Institute of Tropical Medicine
    • Contact: Yven Van Herrewege; Phone Number: +3232476557; Email: yvanherrewege@itg.be
    • Contact: Jorge Reis Guerreiro; Email: jreis@itg.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• BMI >/=18,5 kg/m2 and ≤35 kg/m2
• Agreement to share and discuss participant's medical history and medical records when relevant with the study team
• Able and willing to provide written informed consent
• Agreement to refrain from blood donation and other vaccinations during the study

Exclusion Criteria:

• Participants with a confirmed flavivirus infection in the past
• Participants who received a flavivirus vaccination prior to enrolment (e.g. YFV, Japanese encephalitis virus, tick-borne encephalitis virus, Dengue)
• Receipt of any vaccine (licensed or experimental) within 30 days prior to enrolment or during the study
• Active participation in another interventional clinical study with active substance intake or large medical procedures affecting the study procedures during or 1 month prior to enrolment
• Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC within 24 hours prior to the visit; inclusion at a later date is permitted at the discretion of the investigator
• Any confirmed or suspected immunosuppressive or immunodeficient state (incl. cancer and human immunodeficiency virus/hepatitis B virus infection); asplenia; recurrent severe infections and use of immunosuppressant medication (including antineoplastic and immunomodulating agents or radiotherapy) within the last 6 months prior to enrolment, except topical or short-term oral steroids (<2 weeks of daily receipt of 20 mg of prednisone or equivalent). Refer to annex 1 for a list of immunosuppressive medication
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, psychiatric and neurological illness (mild/moderate well controlled comorbidities are allowed)
• History of bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following venipuncture
• Any significant disease, disorder or planned surgery which may affect the ability of the volunteer to participate in the study or impact (skin) immunity homeostasis
• Suspected or known alcohol or drug dependency
• Known pregnancy
• Tendency to keloid (scar) formation in response to skin damage
• Skin diseases or tattoo at the biopsy site
• In the opinion of the investigator, unlikely compliance to the requirements of the study
• History of thymus dysfunction (including myasthenia gravis, thymoma) or thymectomy
• Individuals who are working at the investigational site or within the research team of this study
• Participants who received immunoglobulins and/or any blood or blood derived products within 3 months preceding the study
• Participants who are currently on anticoagulant therapy
• Participants who are continuously using systemic antivirals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy unvaccinated participants against yellow fever virus; Healthy participants that have not been vaccinated against yellow fever virus	Procedure: Skin punch biopsy; 2 x 4mm skin punch biopsies in the upper arm will be taken from each participant at visit 2 with additional microsampling (microbiopsy and wound blood sampling); Procedure: Blood samples; Blood sampling of 15 mL (10mL Lithium-Heparine + 5 mL SST) is performed on Visit 1 to confirm their vaccination status regarded to yellow fever

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the baseline number and proportion of skin-resident memory T cells against YFV (YFV-TRM) in the skin of unvaccinated and healthy volunteers against YFV	The number and proportion of YFV-specific T cells within the skin-resident lymphocyte parent population at visit 2, measured by flow cytometry.	Day 14 (Visit 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the baseline number and proportion of circulating effector- (YFV-TEM) and central-memory T cells against YFV (YFV-TCM) in the blood of unvaccinated and healthy volunteers against YFV	The number and proportion of circulating YFV-specific TCM and TEM cells within the CD3+ lymphocyte parent population at visit 1	Day 0 (Visit 1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimate the baseline cytokine and chemokine concentrations in peripheral and capillary blood, and microbiopsies of unvaccinated and healthy volunteers against YFV	The number of cytokine and chemokine concentrations (ng/ul) in peripheral and capillary blood, and microbiopsies at visit 2	Day 14 (Visit 2)
Estimate the baseline YFV-specific IgG/IgM levels in peripheral and capillary blood of unvaccinated and healthy volunteers	IgG/IgM levels (mean fluorescence intensity) in peripheral and capillary blood at visit 2	Day 14 (Visit 2)
Describe the spatially-resolved position of TRM cells in the skin of unvaccinated and healthy volunteers against YFV	Spatially-resolved YFV-specific TCR clonotypes in the skin at visit 2	D14 (Visit 2)
Determine the baseline TCR diversity index in the skin of unvaccinated healthy volunteers against YFV	TCR diversity index in the skin at visit 2	Day 14 (Visit 2)

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): November 15, 2026

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Yellow Fever; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: 1966/25

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No